Association of Bile Acid and Pepsin Micro-aspiration with Chronic Obstructive Pulmonary Disease Exacerbation

Background: Chronic Obstructive Pulmonary Disease (COPD) is one of the most common chronic diseases all around the world. One of suggested risk factors for COPD is Gastroesophageal Reflux Disease (GERD). The aim of this study was investigation of the association between micro-aspiration of bile acid and pepsin with exacerbation attacks in COPD patients. Materials and Methods: The present study was a descriptive cross-sectional study. Fifty-two COPD patients were selected by simple sampling from patients referring to the Bessat Lung Clinic. Participants were divided into two groups of with and without COPD exacerbation history in the past year. The severity of the disease was determined based on the GOLD criteria (mild, moderate, severe and very severe). Then, all patients underwent bronchoscopy and the concentrations of bile acid and pepsin were compared in Broncho-Alveolar Lavage Fluid (BALF) of two groups. Results: The mean of bile acids in the group without COPD exacerbations was lower (27.38±3.26 μmol/Lit) than the group with COPD exacerbations (32.31±5.35 μmol/Lit) and this difference was not significant (P=0.436). The mean of pepsin in the first group was higher (118.46 ±15.44 ng/ml) than the second group (107.88±10.7 ng/ml) and this difference was also not significant (P=0.577). Conclusion: According to the results of this study, there is no association between disease severity and number of exacerbations with micro-aspiration of bile acid and pepsin in COPD patients.


World Health Organization (WHO) has defined
Chronic Obstructive Pulmonary Disease (COPD) as a collection of pulmonary diseases that cause irreversible airflow limitation and chronic bronchitis, and emphysema and small airway disease are included in this group (1). In 2015, it was estimated that nearly three million deaths (5% of all deaths) in the world were attributed to COPD, and more than 90% of them occurred in low-and middleincome countries (2) and it was predicted that this disease will be the third leading cause of death in the world by 2020 (1).
Tobacco use is the primary risk factor for COPD and exposure to indoor and outdoor polluted air, as well as occupational dust, are other factors that cause this disease  The mechanisms that affect acute exacerbations in COPD are not understood until now. According to the researches, more than 50% of the cases are due to viral and bacterial respiratory infections, 10% are due to environmental pollutions, and more than 30% are of unknown etiology (3,5).
Gastroesophageal Reflux Disease (GERD) is one of the risk factors that was proposed for COPD exacerbations and also among patients with GERD, upper respiratory symptoms are frequent (4,6 Several studies have been done to investigate the effect of reflux on the increasing of COPD exacerbations (4,(13)(14)(15)(16) and a systematic review and meta-analysis showed GERD is a risk factor for COPD exacerbations (17). In a study in Canada, the results showed that in patients who developed obstructive bronchiolitis following lung transplantation, the prevalence of bile acid micro-aspiration is increased (15). Meanwhile, in another study the authors showed 37% of COPD patients had GER, and the number of COPD exacerbations in patients with GERD was reported two times more than GERD-free patients (2.3 compared to 1.6 in a year) (16).
Regarding the prevalence of GERD in patients with COPD, the aim of this study was to investigate the association of bile acid and pepsin micro-aspiration with COPD exacerbations in Kerman.

MATERIALS AND METHODS
This was an analytical descriptive cross-sectional study.
According to previous studies, the sample size was 52

RESULTS
The mean age in groups of with and without COPD   There was no correlation between micro-aspiration markers with clinical symptoms, FEV1 and BODE index (Table3).

DISCUSSION
It has been shown that GERD and micro-aspiration are common in many chronic respiratory diseases including COPD (19). In all studies, micro-aspiration of bile acid and pepsin was seen (the mean was 29.84±4.30 µmol/Lit) but we did not find any association between amount of microaspiration and number of COPD exacerbations. In the present study, we found bile acid and pepsin in BALF of all patients and with the mean of 29.84±4.30 µmol/Lit and 113.17±13.10 ng/ml, respectively. GERD symptoms compared to those without GERD symptoms (16).
The limitations of this study included loss of control group (because bronchoscopy is an invasive procedure), low sample size and limiting of GERD diagnosis to some questions.

CONCLUSION
According to the results of this study, there was not any association between micro-aspiration of bile acid and pepsin with COPD exacerbations, severity of COPD, BODE-index and GERD symptoms.